The pools are well poised after the first two rounds back in October, with Dragons, Ospreys, Connacht, Zebre and Benetton Rugby all well in the mix for knockout qualification.
Here’s a look at this weekend’s clashes as the sides look to make a winning return to European action.
Enisei-STM v Zebre
After two gritty encounters against Bristol Bears in the opening two rounds of the competition, Zebre sit third in Pool 4 with one win and a loss to their name.
With leaders La Rochelle going up against the aforementioned Bears, Zebre will look to gain ground on their rivals as they prepare to face Russian Champions Enisei-STM.
— Zebre Rugby (@ZebreRugby) December 6, 2018
The Italians will be encouraged by the two heavy defeats that their opponents suffered at the hands of La Rochelle in their opening matches, but must be wary of the toll that the gruelling trip to the Siberian city of Krasnoyarsk could take.
Benetton Rugby v Harlequins
Stadio Comunale di Monigo
The top two in Pool 5 do battle in Treviso on Saturday afternoon as Benetton look to leapfrog their English opponents.
In a finely-poised group, each side have one win and a defeat to their names, with Benetton second by virtue of their bonus-point triumph over Grenoble in round one.
In Harlequins they face a stern test: the Londoners are three-time winners of the tournament and have recently found form in the Gallagher Premiership, but Benetton will look to build on their win at Isuzu Southern Kings last time out as they return to home soil.
Northampton Saints v Dragons
Locked level on five points after their opening two Pool 1 fixtures, the Dragons will look to enact revenge on a Saints side that dealt them a 35-21 defeat at Rodney Parade back in round 2.
— Dragons 🏉 (@dragonsrugby) December 4, 2018
For their part, the Gallagher Premiership side – two-time Challenge Cup winners – have enjoyed a mixed bag domestically as they sit 10th in the league.
Dragons will be keen to shake off last week’s defeat to Leinster, instead taking inspiration from the win over Edinburgh Rugby a fortnight ago as they look to take the initiative in the group’s race for the knockouts.
Connacht v Perpignan
In-form Connacht will fancy their chances as they look to gain ground on Sale Sharks at the top of Pool 3 when they welcome struggling Perpignan to Galway.
The French side are winless from their first two Challenge Cup fixtures and are yet to taste victory in 11 Top 14 outings so far this season after their recent return to the top flight.
Andy Friend’s side will be confident that they can extend their streak, which currently stretches to three wins on the bounce, into European action on Saturday afternoon.
— Ospreys (@ospreys) December 5, 2018
Ospreys v Stade Francais
Another Guinness PRO14 side looking to transfer their form across to the Challenge Cup, Allen Clarke’s Ospreys responded to a heavy defeat at the hands of Leinster to confidently down Zebre last time out.
Their opponents at the Liberty have not won since October in the Top 14 and currently sit bottom of Pool 2, while Ospreys are second behind Worcester Warriors.
A win over the French side – with Worcester going up against third-place Pau – could prove vital for the Welsh province, serving to cement their push for the knockout stages.